Abstract
MicroRNAs (miRNAs) have been reported to have diverse biological roles in regulating many biological processes, including osteogenic differentiation. In the present study, we identified that miR-24 was a critical regulator during osteogenic differentiation. We found that overexpression of miR-24 significantly inhibited osteogenic differentiation, which decreased alkaline phosphatase activity, matrix mineralization and the expression of osteogenic differentiation markers. In contrast, inhibition of miR-24 exhibited an opposite effect. Furthermore, we delineated that miR-24 regulates post-transcriptionals of T-cell factor-1 (Tcf-1) via targeting the 3'-untranslated region (UTR) of Tcf-1 mRNA. MiR-24 was further found to regulate the protein expression of Tcf-1 in the murine osteoprogenitors cells and bone mesenchymal stem cells. Additionally, the positive effect of miR-24 suppression on osteoblast differentiation was apparently abrogated by Tcf-1 silencing. Taken together, our data suggest that miR-24 participates in osteogenic differentiation by targeting and regulating Tcf-1 expression in osteoblastic cells.
Highlights
Osteoblasts and osteoclasts play an important role in regulating bone homeostasis [1]
The results show that miR-24 was downregulated during osteogenic differentiation in mouse bone mesenchymal stem cells (BMSCs)
The results show that miR-24 overexpression significantly decreased the protein expression of T-cell factor-1 (Tcf-1) in BMSCs and
Summary
Osteoblasts and osteoclasts play an important role in regulating bone homeostasis [1]. A reduction in bone mass results in osteoporosis and current treatments generally target osteoclasts to inhibit bone resorption [2]. MiR-302a has been demonstrated to stimulate osteogenic differentiation via targeting and inhibiting chicken ovalbumin upstream promoter transcription factor I which is a potent transcription factor inhibiting osteogenic differentiation [16] These findings provide evidence that targeting miRNA may provide potential and valid therapeutics for the treatment of bone mass loss. The Wnt signaling pathway plays an important role in regulating cell apoptosis, cell growth and differentiation [17]. T-cell factor-1 (Tcf-1) expression has been found to be highly increased in secreted frizzled-related protein-1-null mice with activated Wnt signaling and increased runt-related transcription factor 2 (Runx2) activity [22], the key osteogenic transcription factor for osteogenic differentiation and bone formation [23]. We demonstrate here that miR-24 regulates osteogenic differentiation through targeting and regulating the expression of Tcf-1
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